Application of machine learning algorithms for accurate determination of bilirubin level on in vitro engineered tissue phantom images.

Neonatal Jaundice is a common occurrence in neonates. High excess bilirubin would lead to hyperbilirubinemia, leading to irreversible adverse damage such as kernicterus. Therefore, it is necessary and important to monitor neonates' bilirubin levels in real-time for immediate intervention. However, current screening protocols have their inherent limitations, necessitating more convenient measurements. In this proof-of-concept study, we evaluated the feasibility of using machine learning for the screening of hyperbilirubinemia in neonates from smartphone-acquired photographs. Different machine learning models were compared and evaluated to gain a better understanding of feature selection and model performance in bilirubin determination. An in vitro study was conducted with a bilirubin-containing tissue phantom to identify potential biological and environmental confounding factors. The findings of this study present a systematic characterization of the confounding effect of various factors through separate parametric tests. These tests uncover potential techniques in image pre-processing, highlighting important biological features (light scattering property and skin thickness) and external features (ISO, lighting conditions and white balance), which together contribute to robust model approaches for accurately determining bilirubin concentrations. By obtaining an accuracy of 0.848 in classification and 0.812 in regression, these findings indicate strong potential in aiding in the design of clinical studies using patient-derived images.

Microneedles loaded with cerium-manganese oxide nanoparticles for targeting macrophages in the treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.

Morroniside-mediated mitigation of stem cell and endothelial cell dysfunction for the therapy of glucocorticoid-induced osteonecrosis of the femoral head.

BACKGROUND: Prolonged use of glucocorticoids (GCs) potentially lead to a condition known as GCs-induced osteonecrosis of the femoral head (GIONFH). The primary mechanisms underlying this phenomenon lies in stem cells and endothelial cells dysfunctions. Morroniside, an iridoid glycoside sourced from Cornus officinalis, possesses numerous biological capabilities, including combating oxidative stress, preventing apoptosis, opposing ischemic effects, and promoting the regeneration of bone tissue. PURPOSE: This study aimed to analyze the impact of Morroniside on Dexamethasone (DEX)-induced dysfunction in stem cells and endothelial cells, and its potential as a therapeutic agent for GIONFH in rat models. METHODS: ROS assay, JC-1 assay, and TUNEL assay were used to detect oxidative stress and apoptosis levels in vitro. For the evaluation of the osteogenic capability of bone marrow-derived mesenchymal stem cells, we employed ALP and ARS staining. Additionally, the angiogenic ability of endothelial cells was assessed using tube formation assay and migration assay. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were utilized to evaluate the in vivo therapeutic efficacy of Morroniside. RESULTS: Morroniside mitigates DEX-induced excessive ROS expression and cell apoptosis, effectively reducing oxidative stress and alleviating cell death. In terms of osteogenesis, Morroniside reverses DEX-induced osteogenic impairment, as evidenced by enhanced ALP and ARS staining, as well as increased osteogenic protein expression. In angiogenesis, Morroniside counteracts DEX-induced vascular dysfunction, demonstrated by an increase in tube-like structures in tube formation assays, a rise in the number of migrating cells, and elevated levels of angiogenic proteins. In vivo, our results further indicate that Morroniside alleviates the progression of GIONFH. CONCLUSION: The experimental findings suggest that Morroniside concurrently mitigates stem cell and endothelial cell dysfunction through the PI3K/AKT signaling pathway both in vitro and in vivo. These outcomes suggest that Morroniside serves as a potential therapeutic agent for GIONFH.

Spin skyrmion gaps as signatures of strong-coupling insulators in magic-angle twisted bilayer graphene.

The flat electronic bands in magic-angle twisted bilayer graphene (MATBG) host a variety of correlated insulating ground states, many of which are predicted to support charged excitations with topologically non-trivial spin and/or valley skyrmion textures. However, it has remained challenging to experimentally address their ground state order and excitations, both because some of the proposed states do not couple directly to experimental probes, and because they are highly sensitive to spatial inhomogeneities in real samples. Here, using a scanning single-electron transistor, we observe thermodynamic gaps at even integer moiré filling factors at low magnetic fields. We find evidence of a field-tuned crossover from charged spin skyrmions to bare particle-like excitations, suggesting that the underlying ground state belongs to the manifold of strong-coupling insulators. From the spatial dependence of these states and the chemical potential variation within the flat bands, we infer a link between the stability of the correlated ground states and local twist angle and strain. Our work advances the microscopic understanding of the correlated insulators in MATBG and their unconventional excitations.

Toxic effects of combined exposure to cadmium and nitrate on intestinal morphology, immune response, and microbiota in juvenile Japanese flounder (Paralichthys olivaceus).

Cadmium (Cd2+) and nitrate (NO3-) are important environmental pollutants in the offshore marine ecological environment. However, limited research has explored their combined effects, particularly regarding their impact on the microbiota and intestinal health of marine fish. In this study, juvenile Japanese flounders (P. olivaceus) were immersed in seawater samples with different combinations of Cd2+ (0, 0.2, and 2 mg/L) and NO3- (0 and 80 mg/L NO3N) for 30 days to explore their toxic impacts on intestinal morphology, tight junction (TJ) barrier, immune response, and microbiota. Our results showed that Cd2+ or NO3- exposure alone led to histopathological damage of the gut, while their co-exposure aggravated intestinal damage. Moreover, co-exposure substantially decreased TJ-related gene expression, including occludin, claudin-10, and ZO-2, suggesting increased TJ permeability in the gut. Regarding the immune response, we observed upregulated expression of immune-related markers such as HSP40, IL-1ß, TNF-α, and MT, suggesting the onset of intestinal inflammation. Furthermore, Cd2+ and NO3- exposure led to changes in intestinal microflora, characterized by decreased the abundance of Sediminibacterium and NS3a_marine_group while increasing the prevalence of pathogens or opportunistic pathogens such as Ralstonia, Proteus, and Staphylococcus. This alteration in microbiota composition increased network complexity and α-diversity, ultimately causing dysbiosis in the fish gut. Additionally, combined exposure resulted in metabolic disorders that affected the predicted functions of the intestinal microbiota. Overall, our study demonstrates that Cd2+-NO3- co-exposure amplifies the deleterious effects compared to single exposure. These findings enhance our understanding of the ecological risks posed by Cd2+-NO3- co-exposure in marine ecosystems.

Pharmacological activation of the Nrf2 pathway by Taxifolin remodels articular cartilage microenvironment for the therapy of Osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a widely prevalent degenerative disease marked by extracellular matrix (ECM) degradation, inflammation, and apoptosis. Taxifolin (TAX) is a natural antioxidant possessing various pharmacological benefits, such as combating inflammation, oxidative stress, apoptosis, and serves as a potential chemopreventive agent by regulating genes through an antioxidant response element (ARE)-dependent mechanism. Currently, no studies have investigated the therapeutic impact and precise mechanism of TAX on OA. PURPOSE: The aim of this study is to examine the potential role and mechanism of TAX in reshaping the cartilage microenvironment, thereby offering a stronger theoretical foundation for pharmacologically activating the Nrf2 pathway to manage OA. STUDY DESIGN AND METHODS: The pharmacological effects of TAX were examined in chondrocytes through in vitro studies and in a destabilization of the medial meniscus (DMM) rat model for in vivo analysis. RESULTS: TAX suppresses IL-1ß triggered secretion of inflammatory agents, chondrocyte apoptosis, and ECM degradation, contributing to the remodeling of the cartilage microenvironment. In vivo experiment results demonstrated that TAX counteracted cartilage degeneration induced by DMM in rats. Mechanistic investigations revealed that TAX hinders OA development by reducing NF-κB activation and ROS production through the activation of the Nrf2/HO-1 axis. CONCLUSION: TAX reshapes the articular cartilage microenvironment by suppressing inflammation, mitigating apoptosis, and decreasing ECM degradation through the activation of the Nrf2 pathway. As a result, pharmacological activation of the Nrf2 pathway by TAX holds potential clinical significance in remodeling the joint microenvironment for OA treatment.

Nanoscale multi-beam lithography of photonic crystals with ultrafast laser.

Photonic crystals are utilized in many noteworthy applications like optical communications, light flow control, and quantum optics. Photonic crystal with nanoscale structure is important for the manipulation of light propagation in visible and near-infrared range. Herein, we propose a novel multi beam lithography method to fabricate photonic crystal with nanoscale structure without cracking. Using multi-beam ultrafast laser processing and etching, parallel channels with subwavelength gap are obtained in yttrium aluminum garnet crystal. Combining optical simulation based on Debye diffraction, we experimentally show the gap width of parallel channels can be controlled at nanoscale by changing phase holograms. With the superimposed phase hologram designing, functional structures of complicated channel arrays distribution can be created in crystal. Optical gratings of different periods are fabricated, which can diffract incident light in particular ways. This approach can efficiently manufacture nanostructures with controllable gap, and offer an alternative to the fabrication of complex photonic crystal for integrated photonics applications.

Strongly suppressed diffuse scattering in periodic graphene metamaterials.

As an emerging two-dimensional material, graphene offers an alternative material platform for exploring new metamaterial phenomena and device functionalities. In this work, we examine diffuse scattering properties in graphene metamaterials. We take periodic graphene nanoribbons as a representative example and show that diffuse reflection in graphene metamaterials as dominated by diffraction orders is restricted to wavelengths less than that of first-order Rayleigh anomaly, and is enhanced by plasmonic resonances in graphene nanoribbons, as similar to metamaterials made of noble metals. However, the overall magnitude of diffuse reflection in graphene metamaterial is less than 10-2 due to the large period to nanoribbon size ratio and ultra-thin thickness of the graphene sheet, which suppress the grating effect from the structural periodicity. Our numerical results indicate that, in contrast to the cases of metallic metamaterials, diffuse scattering plays a negligible role in spectral characterization of graphene metamaterials in cases with large resonance wavelength to graphene feature size ratio, which corresponds to typical chemical vapor deposition (CVD)-grown graphene with relatively small Fermi energy. These results shed light on fundamental properties of graphene nanostructures and are helpful in designing graphene metamaterials for applications in infrared sensing, camouflaging, and photodetection, etc.

Visit-to-Visit Blood Pressure Variability and Cardiovascular Outcomes in Patients Receiving Intensive Versus Standard Blood Pressure Control: Insights From the STEP Trial.

BACKGROUND: The clinical prognostic value of visit-to-visit blood pressure (BP) variability (BPV) is debatable, and relative studies among patients receiving BP control to achieve lower BP targets are limited. METHODS: We analyzed a dataset from the STEP trail (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) to investigate the relationship between visit-to-visit BPV and cardiovascular events in patients with hypertensive aged 60 to 80 years. Visit-to-visit BPV was defined as the coefficient of variation, SD, delta, average real variability, and variability independent of the mean of BP measured at 6-, 9-, 12-, 15-, and 18-month follow-up visits. We computed hazard ratios for the risks associated with a 1-SD increase in BPV indexes in multivariable cox regression models. RESULTS: Among 7678 patients from the STEP trial, after adjustment for multiple confounders, diastolic BPV indexes were significantly associated with the primary composite end point (hazard ratios ≥1.21; P≤0.029) in the standard group, while there was no association between the clinical outcomes and systolic BPV (P≥0.091). In the intensive treatment group, either systolic or diastolic BPV was no association with clinical outcomes(P≥0.30). Sensitivity analyses using an alternative method to calculate BPV based on 7 BP records generated confirmatory results. CONCLUSIONS: In older adults with hypertension, visit-to-visit diastolic BPV is an independent predictor of adverse health outcomes in the standard treatment group. However, BPV did not have prognostic value in the intensive treatment group. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03015311.

Fluorescence enhancement of organic dyes by femtosecond laser-induced cavitation bubbles for crystal imaging.

Fluorescence from organic dyes can be applied in many research fields such as imaging, bio-sensing and diagnosis. One shortcoming of fluorescence imaging is the limitation in emission intensity. Amplification of fluorescence signals can be achieved by the enhancement of localized electromagnetic fields. Metallic nanoparticles are widely applied to produce plasmon resonance, but they cause thermal damage to fragile bio-materials. In this study, we propose a method for nanoparticle-free fluorescence enhancement by ultrafast laser-induced cavitation bubbles in organic dye solutions. Fluorescence enhancement without the use of nanoparticles prevents potential hazards including thermal effects and biotoxicity. In order to achieve fluorescence enhancement in neat dye solution, cavitation bubbles were induced by focusing an 800 nm ultrafast laser beam. Another 400 nm laser beam was used to pump the gain medium. Fluorescence enhancement was observed in various dye solutions. The intensity and spectra of the fluorescence emission can be controlled by changing the power and focus of the excitation laser. According to time-resolved microscopy and simulation results, the cavity formed by the laser-induced bubbles results in the enhancement of the localized electromagnetic field and induces the amplification of the fluorescence signal. The bubble-enhanced fluorescence emission was used for imaging of protein crystals without causing thermal damage to the samples. This study provides an effective method for bio-compatible fluorescence enhancement and has application prospects in fields such as bio-imaging.

Tunable spin and valley excitations of correlated insulators in Γ-valley moiré bands.

Moiré superlattices formed from transition metal dichalcogenides support a variety of quantum electronic phases that are highly tunable using applied electromagnetic fields. While the valley degree of freedom affects optoelectronic properties in the constituent transition metal dichalcogenides, it has yet to be fully explored in moiré systems. Here we establish twisted double-bilayer WSe2 as an experimental platform to study electronic correlations within Γ-valley moiré bands. Through local and global electronic compressibility measurements, we identify charge-ordered phases at multiple integer and fractional moiré fillings. By measuring the magnetic field dependence of their energy gaps and the chemical potential upon doping, we reveal spin-polarized ground states with spin-polaron quasiparticle excitations. In addition, an applied displacement field induces a metal-insulator transition driven by tuning between Γ- and K-valley moiré bands. Our results demonstrate control over the spin and valley character of the correlated ground and excited states in this system.

Alterations of Gut Microbiome, Metabolome, and Lipidome in Takayasu Arteritis.

OBJECTIVE: Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune-related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK. METHODS: To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes. RESULTS: A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK. CONCLUSION: This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome-metagenome interface in TAK subtype prediction and pathogenesis are suggested.

Acute low-dose phosphate disrupts glycerophospholipid metabolism and induces stress in juvenile turbot (Scophthalmus maximus).

Phosphate, as the main nutrient factor of lake eutrophication brought by pollutants discharged from agriculture and industry, is always considered to be a low-toxicity substance to aquatic animals. But the toxicity mechanism is unclear, and published information is limited. In this study, a 96 h acute stress experiment was conducted on juvenile turbot (Scophthalmus maximus) with 0, 10, and 60 mg/L phosphate solutions. Metabonomic analysis revealed that low-dose phosphate (10 mg/L) disrupted glycerophospholipid, purine, and glycolipid metabolism, as well as the tricarboxylic acid (TCA) cycle in juveniles, even at 96 h of stress, which may lead to cell structure damage and signal recognition disorder between cells. Upregulated key genes in the main glycerophospholipid metabolic pathways, which matched the results of the metabolomic study, were detected. Furthermore, low-dose phosphate (10 mg/L) induced oxidative stress and immunotoxicity in fish, resulting in the raising of relevant genes expression such as cat and sod in liver and kidney. In addition, all phosphate-treated groups had induced lesions on gill tissue, as evidenced by pathological observations. In this study on toxic effects on and mechanism of phosphate in aquatic animals using metabolomics, gene expression, and histopathology, we confirm that acute low-dose phosphate could disrupt glycerophospholipid metabolism and induce stress in juvenile turbot. This can provide advice on the amount of phosphate accumulation for marine fish farming and on protecting species diversity and marine ecosystem from the point of view of phosphate toxicity to marine animals.

Smart nanogels for cancer treatment from the perspective of functional groups.

Introduction: Cancer remains a significant health challenge, with chemotherapy being a critical treatment modality. However, traditional chemotherapy faces limitations due to non-specificity and toxicity. Nanogels, as advanced drug carriers, offer potential for targeted and controlled drug release, improving therapeutic efficacy and reducing side effects. Methods: This review summarizes the latest developments in nanogel-based chemotherapy drug delivery systems, focusing on the role of functional groups in drug loading and the design of smart hydrogels with controlled release mechanisms. We discuss the preparation methods of various nanogels based on different functional groups and their application in cancer treatment. Results: Nanogels composed of natural and synthetic polymers, such as chitosan, alginate, and polyacrylic acid, have been developed for chemotherapy drug delivery. Functional groups like carboxyl, disulfide, and hydroxyl groups play crucial roles in drug encapsulation and release. Smart hydrogels have been engineered to respond to tumor microenvironmental cues, such as pH, redox potential, temperature, and external stimuli like light and ultrasound, enabling targeted drug release. Discussion: The use of functional groups in nanogel preparation allows for the creation of multifunctional nanogels with high drug loading capacity, controllable release, and good targeting. These nanogels have shown promising results in preclinical studies, with enhanced antitumor effects and reduced systemic toxicity compared to traditional chemotherapy. Conclusion: The development of smart nanogels with functional group-mediated drug delivery and controlled release strategies represents a promising direction in cancer therapy. These systems offer the potential for improved patient outcomes by enhancing drug targeting and minimizing adverse effects. Further research is needed to optimize nanogel design, evaluate their safety and efficacy in clinical trials, and explore their potential for personalized medicine.

Ancient homomorphy of molluscan sex chromosomes sustained by reversible sex-biased genes and sex determiner translocation.

Contrary to classic theory prediction, sex-chromosome homomorphy is prevalent in the animal kingdom but it is unclear how ancient homomorphic sex chromosomes avoid chromosome-scale degeneration. Molluscs constitute the second largest, Precambrian-originated animal phylum and have ancient, uncharacterized homomorphic sex chromosomes. Here, we profile eight genomes of the bivalve mollusc family of Pectinidae in a phylogenetic context and show 350 million years sex-chromosome homomorphy, which is the oldest known sex-chromosome homomorphy in the animal kingdom, far exceeding the ages of well-known heteromorphic sex chromosomes such as 130-200 million years in mammals, birds and flies. The long-term undifferentiation of molluscan sex chromosomes is potentially sustained by the unexpected intertwined regulation of reversible sex-biased genes, together with the lack of sexual dimorphism and occasional sex chromosome turnover. The pleiotropic constraint of regulation of reversible sex-biased genes is widely present in ancient homomorphic sex chromosomes and might be resolved in heteromorphic sex chromosomes through gene duplication followed by subfunctionalization. The evolutionary dynamics of sex chromosomes suggest a mechanism for 'inheritance' turnover of sex-determining genes that is mediated by translocation of a sex-determining enhancer. On the basis of these findings, we propose an evolutionary model for the long-term preservation of homomorphic sex chromosomes.

Guided-mode resonance with reduced bandwidth in mid-infrared absorption and thermal emission.

Narrowband resonance plays an important role in many optical applications, especially for the development of wavelength-selective properties and enhanced light-matter interaction. In this paper, we demonstrate metal-insulator-metal (MIM) waveguide gratings, which exhibit guided-mode resonance (GMR) with reduced bandwidth in mid-infrared absorption and thermal emission. Our fabricated MIM waveguide grating consists of a copper substrate, a lossless ZnSe film, and a top gold stripe grating. Our measurements reveal strong GMRs with a bandwidth of 1.29% of the central wavelength in both mid-infrared absorption and thermal emission spectra. By varying structural parameters of the MIM waveguide grating, strong absorptions and thermal emissions of GMRs are observed and tuned within the 3-5 µm wavelength range. These results manifest the great potential of engineering infrared properties by using GMR and could be useful for spectral control in a variety of infrared devices.

Exposure to nitrate induces alterations in blood parameter responses, liver immunity, and lipid metabolism in juvenile turbot (Scophthalmus maximus).

Nitrate (NO3-) pollution of waterbodies has attracted significant global attention as it poses a serious threat to aquatic organisms and human beings. This study aimed to evaluate the role of NO3-, an end product of biological nitrification processes, in immune status and lipid metabolism to have a comprehensive understanding of its toxic effects on fishes. Therefore, in this work, juvenile turbot (Scophthalmus maximus) were subjected to four nominal concentrations of NO3- (i.e., 0, 50, 200, 400 mg/L of NO3--N) for a 60-day period. The results indicated that increased exposure to NO3- (200 and/or 400 mg/L) enhanced the concentrations of plasma heat shock protein concentrations (HSP70), complement component 3 (C3), complement component 4 (C4), immunoglobulin M (IgM) and lysozyme (LYS), which meant that NO3-caused fluctuations in the plasma immune system. Higher exposure to NO3- (200 and/or 400 mg/L) also caused significant enhancements in plasma glutamic pyruvic transaminase (GPT), as well as glutamic oxaloacetic transaminase (GOT) activity. Furthermore, NO3- exposure resulted in upregulation of liver TNF-α, IL-1ß, HSP70, HSP90, and LYS. Additionally, the results suggested that NO3-exposure caused a certain degree of histological damage and inflammation in the liver and activated the immune defense processes of juvenile turbot. Furthermore, the mRNA expression levels of certain genes associated with lipid metabolism (peroxisome proliferator-activated receptor-alpha [PPAR-α], carnitine palmitoyltransferase 1[CPT1], liver X receptor [LXR] together with sterol regulatory element binding protein-1 [SREBP-1]) increased significantly within fish liver exposed to 200/400 mg/L NO3--N treatments. Finally, the results obtained from the analysis of the integrated biological responses version 2 (IBRv2) also confirmed the toxic effects of NO3- on juvenile turbot. According to these findings, it can be found that NO3- emission in the aquatic environment needs to be strictly controlled, as it may cause immune and lipid metabolism disorders in fish.

Validating transdermal alcohol biosensors: a meta-analysis of associations between blood/breath-based measures and transdermal alcohol sensor output.

BACKGROUND AND AIMS: Transdermal alcohol sensors carry immense promise for the continuous assessment of drinking but are inconsistent in detecting more fine-grained indicators of alcohol consumption. Prior studies examining associations between transdermal alcohol concentration (TAC) and blood/breath alcohol concentration (BAC) have yielded highly variable correlations and lag times. The current review aimed to synthesize transdermal validation studies, aggregating results from more than three decades of research to characterize the validity of transdermal sensors for assessing alcohol consumption. METHODS: Databases were searched for studies listed prior to 1 March 2022 that examined associations between transdermal alcohol sensor output and blood and breath-based alcohol measures, resulting in 31 primarily laboratory-derived participant samples (27 precise effect sizes) including both healthy and clinical populations. Correlation coefficients and lag times were pooled using three-level random-effects meta-regression. Independent raters coded study characteristics, including the body position of transdermal sensors (ankle- versus arm/hand/wrist-worn device) and methodological bias (e.g. missing data). RESULTS: Analyses revealed that, in this primarily laboratory-derived sample of studies, the average correlation between TAC and BAC was large in magnitude [r = 0.87, 95% confidence interval (CI) = 0.80, 0.93], and TAC lagged behind BAC by an average of 95.90 minutes (95% CI = 55.50, 136.29). Device body position significantly moderated both TAC-BAC correlation (b = 0.11, P = 0.009) and lag time (b = -69.41, P < 0.001). Lag times for ankle-worn devices were approximately double those for arm/hand/wrist-worn devices, and TAC-BAC correlations also tended to be stronger for arm/hand/wrist-worn sensors. CONCLUSIONS: This meta-analysis indicates that transdermal alcohol sensors perform strongly in assessing blood/breath alcohol concentration under controlled conditions, with particular promise for the newer generation of wrist-worn devices.

Investigation of the influence of blade configuration on the hemodynamic performance and blood damage of the centrifugal blood pump.

PURPOSE: The design and optimization of centrifugal blood pumps are crucial for improved extracorporeal membrane oxygenation system performance. Secondary flow passages are common in centrifugal blood pumps, allowing for a high volume of unstable flow. Traditional design theory offers minimal guidance on the design and optimization of centrifugal blood pumps, so it's critical to understand how design parameter variables affect hydraulic performance and hemocompatibility. METHODS: Computational fluid dynamics (CFD) was employed to investigate the effects of blade number, blade wrap angle, blade thickness, and splitters on pressure head, hemolysis, and platelet activation state. Eulerian and Lagrangian features were used to analyze the flow fields and hemocompatibility metrics such as scalar shear stress, velocity distribution, and their correlation. RESULTS: The equalization of frictional and flow losses allow impellers with more blades and smaller wrap angles to have higher pressure heads, whereas the trade-off between the volume of high scalar shear stress and exposure time allows impellers with fewer blades and larger blade wrap angles to have a lower HI; there are configurations that increase the possibility of platelet activation for both number of blades and wrap angles. The hydraulic performance and hemocompatibility of centrifugal blood pumps are not affected by blade thickness. Compared to the main blades, splitters can improve the blood compatibility of a centrifugal blood pump with a small reduction in pressure head, but there is a trade-off between the length and location of the splitter that suppresses flow losses while reducing the velocity gradient. According to correlation analysis, pressure head, HI, and the volume of high shear stress were all substantially connected, and exposure time had a significant impact on HI. The platelet activation state was influenced by the average scalar shear stress and the volume of low velocity. CONCLUSION: The findings reveal the impact of design variables on the performance of centrifugal blood pumps with secondary flow passages, as well as the relationship between hemocompatibility, hydraulic performance, and flow characteristics, and are useful for the design and optimization of this type of blood pump, as well as the prediction of clinical complications.

Investigation of M2 macrophage-related gene affecting patients prognosis and drug sensitivity in non-small cell lung cancer: Evidence from bioinformatic and experiments.

Background: The progression process of lung cancer can be accelerated by M2 macrophages. However, genes that affect M2 macrophage polarization remain unidentified. Methods: The Cancer Genome Atlas, Gene Expression Omnibus, and Arrayexpress databases were used to obtain open-access data. The analysis of public data was mostly performed with R studio. The RNA levels of specific genes were detected using quantitative real-time PCR. The proliferation ability of the cells was assessed by CCK8, colony formation, and EdU assays. Results: Based on the multiple datasets, we noticed a poor prognosis in patients with high M2 macrophage infiltration. There were 114 genes differentially expressed between high and low M2 macrophages infiltrated samples, regarded as M2 macrophage-related genes. Subsequently, a prognosis prediction signature consisting of ABHD5, HS3ST2, TM6SF1, CAPZA2, LEPROT, HNMT, and MRO was identified and presented a satisfactory performance. The pathway enrichment results revealed a positive correlation between riskscore and enrichment scores for most immunotherapy-related positive terms. Also, there might be an increase in genomic instability among patients at high risk. Interestingly, low risk patients are most likely to benefit from PD-1 therapy, while high risk patients may benefit from CTLA-4 therapy. Meanwhile, the estimated IC50 of seven drugs differs significantly between two risk groups, including Cisplatin, Docetaxel, Doxorubicin, Gefitinib, Paclitaxel, Sunitinib and Vinorelbine. Moreover, further experiments indicated that HNMT was overexpressed and can enhance the proliferation ability in lung cancer cells. Conclusions: In summary, our study identified the molecules significantly affecting M2 macrophage infiltration and identified a prognosis signature that robustly indicated patients prognosis. Moreover, we validated the cancer-promoting effect of HNMT using in vitro experiments.